Volume 1 Supplement 1

Abstracts of the 28th Annual Scientific Meeting of the Society for Immunotherapy of Cancer (SITC)

Open Access

High frequency of HLA class I antigen processing machinery (APM) component upregulation in primary hepatocellular carcinoma tumors

  • Fabio Grizzi1,
  • Barbara Franceschini2,
  • Sonia Di Biccari2,
  • Paola Bossi3,
  • Maurizio Chiriva-Internati4 and
  • Soldano Ferrone5
Journal for ImmunoTherapy of Cancer20131(Suppl 1):P264

DOI: 10.1186/2051-1426-1-S1-P264

Published: 7 November 2013

Malignant transformation of cells is associated with downregulation of HLA class I APM components in most of the tumors. These defects are clinically relevant, since they are frequently associated with the clinical course of the disease. Only in a few tumors malignancy is associated with the upregulation of HLA class I antigens. Among them is hepatocellular carcinoma (HCC). The frequency of HLA class I APM component upregulation and its clinical significance in HCC are not known. These topics were investigated in the present study, since the resulting information may contribute to assess the therapeutic efficacy of T cell-based immunotherapy for the treatment of HCC. Twenty-one surgically resected primary HCC tumors and autologous adjacent non-malignant tissues were stained with a unique panel of monoclonal antibodies which recognize HLA class I APM components. The staining patterns of the malignant tumors were compared to those of the autologous non malignant tissues. To assess the functional significance of changes in HLA class I APM component expression in HCC tumors, the results of immunohistochemical staining were correlated with the extent of CD8+ cytotoxic T-lymphocyte infiltrate, quantified with a computer-aided image analysis system. In all the HCC tumors, malignant hepatocytes expressed high levels of HLA class I APM components. In contrast these molecules were not detected in normal hepatocytes, although they displayed a low expression in some apparently normal hepatocytes adjacent to the HCC tumor. The HLA class I APM component upregulation in HCC was associated with the extent of CD8+ T cell infiltrate, although this association did not reach the level of statistical significance. Our results corroborate the information in the literature about the lack of HLA class I antigen expression in hepatocytes. Furthermore our study shows for the first time that APM components are also not detectable in normal hepatocytes. Lastly our study shows that HLA class I APM component upregulation is very frequent in HCC. Its association with T cell infiltrate, although not statistically significant, is compatible with the possibility that HCC cells are recognized by CD8+ T cells. If so, HCC should represent an attractive target to apply T cell-based immunotherapy.

Authors’ Affiliations

(1)
Laboratory of Molecular Gastroenterology, Humanitas Clinical and Research Center
(2)
Laboratory of Quantitative Medicine, Humanitas Clinical and Research Center
(3)
Department of Pathology, Humanitas Clinical and Research Center
(4)
Department of Internal Medicine, Texas Tech University Health Science Center Medical School
(5)
Department of Surgery, Massachusetts General Hospital, Harvard Medical School

Copyright

© Grizzi et al; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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